Weight Loss Without Muscle Loss: How Myostatin Inhibitors Will Transform Mounjaro and Ozempic Treatment

You've lost 15 kilograms. The scale shows your dream number. But somehow the reflection in the mirror isn't satisfying—your face looks tired, your arms seem thinner, and you have less energy than before starting the program.

This isn't your imagination. It's the reality thousands of people on GLP-1 therapy face. And finally, a solution has emerged that could change everything.

Why Mounjaro and Ozempic Melt More Than Just Fat

When you lose weight—regardless of the method—your body doesn't lose only fat. Part of the weight comes from muscle mass, water, and bone tissue. And that's normal. The problem is how large that portion is.

According to clinical studies, when using semaglutide (Ozempic), 30% to 40% of lost weight may be lean mass [1]. In the STEP 1 study, this figure was approximately 39–40% [1]. With tirzepatide (Mounjaro), the situation is somewhat better—approximately 25–30% of lost weight [18].

But let's translate percentages into kilograms. If you lost 15 kg on Ozempic, about 5–6 kg of that isn't fat. It's your muscles, organs, and tissues responsible for metabolism.

Why does this matter? Skeletal muscles aren't just about appearance. They're central to glucose utilization, insulin sensitivity, and basal metabolism [1]. Muscle loss can leave a person lighter but in a worse metabolic state than before starting treatment.

And this is where it gets interesting. Scientists have found a way to make the body lose primarily fat while preserving muscle.

What Is Myostatin and Why Blocking It Preserves Muscle

Myostatin is a protein your body produces to limit muscle growth. Sounds counterintuitive? Evolutionarily, this made sense: muscles require a lot of energy, and the body conserved resources.

But when you're losing weight, myostatin becomes a problem. It "allows" the body to break down muscle tissue for energy instead of preserving it.

Myostatin inhibitors block this mechanism. When myostatin can't bind to its receptors, the body receives a signal: "Preserve muscle, burn fat."

Apitegromab is a fully human monoclonal antibody that selectively inhibits myostatin activation and can thereby increase muscle mass [3]. Unlike other drugs in this class, it works very selectively—blocking specifically myostatin without affecting other signaling pathways [8].

How does apitegromab differ from bimagrumab? The key difference is selectivity. Apitegromab specifically targets myostatin, while bimagrumab blocks activin type II receptors, affecting a broader spectrum of pathways [8]. This may mean fewer side effects with comparable efficacy.

Apitegromab and the EMBRAZE 2026 Study—A Breakthrough in Nature Medicine

In June 2026, the journal Nature Medicine published results that could change the approach to obesity treatment. The randomized double-blind placebo-controlled Phase 2 EMBRAZE study examined the combination of tirzepatide with apitegromab [3].

The study design was straightforward: 102 adults with overweight or obesity were randomized 1:1 to receive tirzepatide plus apitegromab (10 mg/kg) or tirzepatide plus placebo [3].

The results are impressive:

Note the last row. Total weight loss was virtually the same—a difference of only 1.1%. But the composition of that loss is fundamentally different [2].

In the apitegromab group, 85% of lost weight was fat and only 15% was lean mass. In the placebo group—70% fat and 30% lean mass [5]. This means twice the quality of weight loss.

"The results confirmed our hypothesis that the platform of highly selective myostatin inhibitors has the potential to support healthier weight loss for millions of patients on GLP therapy, safely preserving lean mass" [5] — stated Akshay Vaishnaw, President of Research at Scholar Rock.

Bimagrumab and Other Myostatin Inhibitors in Development

Apitegromab isn't the only player in the field. Bimagrumab from Novartis already has a longer research history and demonstrates interesting results.

Bimagrumab is a human monoclonal antibody that blocks activin type II receptors (ActRIIA and ActRIIB), thereby inhibiting the binding of myostatin and related ligands [38]. It binds to ActRIIB approximately 200 times more strongly than to ActRIIA and has shown induction of skeletal muscle hypertrophy of 7% when administered in vivo [38].

In the BELIEVE study published in Nature Medicine in 2026, the combination of bimagrumab with semaglutide demonstrated significant fat mass loss while preserving lean mass [19].

Key BELIEVE results at week 48:

• Lean mass change: +1.0% to +1.1% (bimagrumab mono), -4.7% to -6.9% (semaglutide mono), -0.8% to -2.3% (combination) [19]
• The combination group of bimagrumab 30 mg/kg + semaglutide 1.0 mg showed the greatest preservation of lean mass [19]

Earlier, in 2020, a bimagrumab study in patients with type 2 diabetes showed: the bimagrumab group gained 3.6% lean mass (1.70 kg), while the placebo group lost 0.8% [15].

Other companies are also actively working in this direction. Regeneron is developing a combination of trevogrumab and garetosmab to block both myostatin and activin A [31]. In the COURAGE study, this combination preserved up to 81% of lean mass compared to semaglutide alone [13].

Myostatin Inhibitor + Mounjaro Combination: What It Will Provide

Let's imagine a practical scenario. You're on the Mounjaro program. Expected weight loss—approximately 20% over a year. With the traditional approach, about 25–30% of this weight will be lean mass.

Now add a myostatin inhibitor. According to EMBRAZE data, you can reduce lean mass loss by half—to 15% [2]. This means:

• More preserved muscle to support metabolism
• Lower risk of sarcopenia and weakness
• Better appearance at the same number on the scale
• Likely lower risk of weight regain after therapy ends

"GLP therapies have been an effective and important innovation for people with obesity and cardiometabolic disorders; however, these drugs can lead to substantial muscle mass loss, creating undesirable health risks" [2] — noted Dr. Vaishnaw.

The mechanism of action of myostatin inhibitors differs from GLP-1 agonism. Instead of affecting appetite or gastric emptying, apitegromab works directly at the muscle tissue level [1]. This makes the combination logical—two drugs complement each other by working through different pathways.

Apitegromab concentrations and total latent myostatin (a pharmacodynamic marker) increased over time and reached a plateau at approximately 16 weeks [3]. This means the effect accumulates gradually and stabilizes.

Limitations: Why Phase 2 Isn't a Prescription Yet

Before planning future treatment, it's important to understand the limitations of available data.

First, sample size. EMBRAZE included only 102 participants [3]. This is sufficient for proof-of-concept but insufficient for conclusions about rare side effects or efficacy in different patient subgroups.

Second, duration. 24 weeks is six months. We don't know what happens to muscle mass with longer use, or whether the effect persists after stopping therapy.

Third, the myostatin inhibitor class has a history of mixed results [14]. Not all molecules that block myostatin have proven successful in clinical trials. Apitegromab showed promising data, but the path to approval is still long.

Regarding safety: the frequency of adverse events was generally similar in both groups—76% (39 of 51) in the apitegromab group and 71% (36 of 51) in the placebo group [3]. Serious adverse events were balanced: one participant (2%) in each group [3].

Scholar Rock plans to continue development of SRK-439—a subcutaneous anti-myostatin antibody for treating cardiometabolic disorders, including obesity [34].

What You Can Do Right Now to Preserve Muscle

Myostatin inhibitors are the future. But there are strategies that work today. And they're free.

Protein: How Much and When

Achieving protein goals of 1.2–1.6 g/kg/day (≈ 0.54–0.73 g/lb/day) and performing resistance training 2–3 times per week helps preserve and even build lean mass [22]. With adequate protein intake and resistance training, lean mass loss can be reduced to 15–25% of total weight lost [33].

For a person weighing 80 kg, this means 96–128 g of protein daily. Distribute it evenly across 3–4 meals.

Resistance Training: Why It's Critical

Studies show that reduced exercise tolerance is associated with greater lean mass reduction in both groups—on semaglutide and tirzepatide [12]. The effect was more pronounced among patients on tirzepatide.

"If you're not exercising when taking these medications, you're essentially..." [12] — researchers warn. Regular resistance exercises 2–3 times per week is the minimum for muscle preservation.

Peptides for Muscle Mass Support

Some peptides can support muscle tissue during weight loss. MOTS-c improves muscle cell metabolism. Tesamorelin stimulates growth hormone production, which positively affects body composition.

Learn more about muscle preservation strategies in our article how to preserve muscle on Mounjaro and Ozempic.

When This Technology Will Become Available

Apitegromab was originally developed for patients with spinal muscular atrophy (SMA) [30]. This is the direction in which Scholar Rock plans to submit a registration application.

Regarding obesity applications—the company announced closure of the EMBRAZE study and continuation of SRK-439 development [34]. SRK-439 is a subcutaneous form of anti-myostatin antibody that may be more convenient for patients.

Other companies are also moving forward. iBio plans to advance its myostatin inhibitor IBIO-600 to Phase 1 in early 2026 [37]. The company focuses on preventing muscle loss after discontinuation of GLP-1 therapy [37].

Realistic forecast: if Phase 3 trials begin in 2026–2027, commercially available myostatin inhibitors for combination with GLP-1 may appear no earlier than 2029–2030.

What should you do now? Proven methods for muscle preservation today are protein and resistance training [8]. They're not as dramatic as an injection of a new drug, but they work and are available to everyone.

What This Means for You

We are on the threshold of a new era in obesity treatment. The first stage of the revolution—GLP-1 drugs like Mounjaro and Ozempic—is already here. The second stage—combination therapies that preserve muscle—is coming.

The EMBRAZE study proved the concept: it's possible to lose weight while preserving most muscle mass. 54.9% better lean mass preservation isn't theoretical calculations—it's the result of a controlled clinical trial [3].

But until these technologies become available, the best strategy is to combine effective GLP-1 therapy with basic principles: adequate protein and regular resistance exercises.

Browse our peptide catalog for muscle tissue support during your weight loss program. Or schedule a consultation to discuss the optimal approach for you.